Involvement of A2B receptor in DNA damage response and radiosensitizing effect of A2B receptor antagonists on mouse B16 melanoma

Yuta Tanaka, Kazuki Kitabatake, Ryo Abe, Mitsutoshi Tsukimoto

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

It is therapeutically important to elucidate the factors involved in the radiation resistance of tumors. We previously showed that ATP is released from mouse melanoma B16 cells in response to γ-irradiation, but the role of adenosine, a metabolite of ATP, is still unclear. Here, we show that the adenosine A2B receptor is involved in DNA damage repair and radioresistance in mouse melanoma B16 cells. The DNA damage response after γ-irradiation was attenuated by pretreatment with A2B receptor antagonists, such as PSB603, while it was enhanced by pretreatment with A2B receptor agonists, such as BAY60-6583. γ-Irradiation decreased the cell survival rate, and pretreatment with PSB603 further reduced the survival rate. On the other hand, pretreatment with BAY60-6583 increased the cell survival rate after irradiation. The DNA damage response and the cell survival rate after γ-irradiation were both decreased in A2B-knockdown cells. In vivo experiments in mice confirmed that tumor growth was suppressed and delayed in the irradiated group pretreated with PSB603, compared with the irradiation-alone group. Our results indicate that adenosine A2B receptor contributes to radioresistance, and could be a new target for the development of agents to increase the efficacy of radiotherapy.

Original languageEnglish
Pages (from-to)516-525
Number of pages10
JournalBiological and Pharmaceutical Bulletin
Volume43
Issue number3
DOIs
Publication statusPublished - 1 Mar 2020

Keywords

  • A2B receptor
  • Adenosine
  • DNA repair
  • Melanoma
  • Radiation therapy
  • γ-irradiation

Fingerprint Dive into the research topics of 'Involvement of A2B receptor in DNA damage response and radiosensitizing effect of A2B receptor antagonists on mouse B16 melanoma'. Together they form a unique fingerprint.

Cite this